Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case–control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein–Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P = 0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P = 0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P = 0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset behavioral disorder with a definite genetic component. The search for genes predisposing to ADHD has focused on genes involved in the regulation of monoamine systems. In this study, we emphasized genes that underlie various aspects of dopamine, norepinephrine and serotonin neurotransmissions and performed a comprehensive association analysis by screening with 245 single-nucleotide polymorphisms (SNPs) of 23 candidate genes in a sample of Chinese Han descent. A total of 182 DSM-IV ADHD children and 184 healthy controls were genotyped and analyzed with an average density of one SNP every 6.1 kb. Both single-SNP and multimarker haplotype analyses were implemented to exploit association signal for ADHD and its diagnostic subtypes. Empirical P-values were derived on the basis of 5000 permutations to evaluate gene-wide statistical significance. MAOA yielded highly suggestive evidence of association (empirical P < 0.01, OR = 1.94) with ADHD. For inattentive ADHD, MAOA, DDC and SYP showed suggestive evidence of association (empirical P < 0.05). ADRA2C achieved suggestive significance (empirical P < 0.05) for ADHD combined type. Additionally, for six genes (SNAP25, NET1, DBH, CHRNA4, DRD3 and SYT1) we detected one or more SNPs with nominal P-valuesp0.05. This study has identified several genes as promising susceptibility loci for ADHD. Replication efforts and further investigations remain necessary to provide definite proof of association.

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Studies of brain alterations in children with attention-deficit/hyperactivity disorder (ADHD) have shown heterogeneous results. The aims of the current study were to investigate white matter microstructure in children using both categorical and dimensional definitions of ADHD and to determine the functional consequences of observed alterations. In a large single-site sample of children (aged 8-15 years) with ADHD (n = 83) and healthy controls (n = 122), we used tract-based spatial statistics on diffusion tensor imaging data to investigate whole-skeleton differences of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD), and mode of anisotropy related to ADHD status (categorical) and symptom severity (dimensional). For categorical differences observed, we analyzed their association with cognitive functioning in working memory and inhibition. Compared with healthy controls, children with ADHD showed decreased FA and increased RD in widespread, overlapping brain regions, mainly in corpus callosum (CC) and major tracts in the left hemisphere. Decreased FA was associated with inhibition performance in the participants with ADHD. Using dimensional definitions, greater hyperactivity/ impulsivity symptom severity was associated with higher FA also in widespread regions, mainly in CC and major tracts in the right hemisphere. Our study showed white matter alterations to be related to ADHD status and symptom severity in patients. The coexistence of decreased FA and increased RD in the absence of alterations in MD or AD might indicate altered myelination as a pathophysiological factor in ADHD.